Increases of cerebellar cGMP content without changes of cAMP were measured after chemical stimulation of the climbing of mossy fiber systems. Lesion of the climbing fiber system with 3-acetyl-pyridine blocks the increase of cGMP produced by harmaline (a selective activator of the olivo-cerebellar pathway) but leaves unabated the increase of cGMP produced by glutamic acid (a exitatory putative amino acid transmitter) or by isoniazid (a drug that decreases GABA levels). Apomorphine increases cerebellar cGMP and haloperidol or morphine decreases cerebellar cGMP when injected in striatum but not in cerebellum, whereas diazepam decreases cerebellar cGMP when injected in cerebellum but not in striatum. These results suggest that two excitatory transmitters released by the parallel or climbing fibers and GABA released by cerebellar interneurons are independently involved in changing cGMP content on the molecular layer of cerebellum. The molecular mechanism of the message mediated by the increase of cGMP is presently being studied. BIBLIOGRAPHIC REFERENCES: Biggio, G. and Guidotti, A.: Regulation of 3',5'-cyclic guanosine monophosphate (cGMP) in cerebellum by a striatal dopaminergic mechanism. Nature 265: 240-242, 1977. Biggio, G., Costa, E. and Guidotti, A.: Pharmacologically induced changes in the 3',5'-cyclic GMP content in rat cerebellar cortex: Difference between appomorphine, haloperidol and harmaline. J. Pharmacol. Exp. Ther. 200: 207-215, 1977.